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Ion channel modulation of chondrocyte cell volume regulation (1182.1)
Author(s) -
Lewis Rebecca,
BarrettJolley Richard
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1182.1
Subject(s) - chemistry , trpv4 , iberiotoxin , patch clamp , transient receptor potential channel , channel blocker , potassium channel , membrane potential , biophysics , ion channel , bumetanide , hyperpolarization (physics) , electrophysiology , bk channel , medicine , microbiology and biotechnology , ion transporter , receptor , biochemistry , biology , membrane , calcium , stereochemistry , organic chemistry , nuclear magnetic resonance spectroscopy
Healthy chondrocytes exist with depolarised resting membrane potentials ( Vm ); critical for volume regulation. Chondrocytes express several cell volume regulation channels, including Transient Receptor Potential (TRP) V4, V5 and V6 and epithelial sodium channels. We investigated mechanisms of cell volume regulation in healthy chondrocytes. Patch clamp electrophysiology was used to measure canine chondrocyte Vm ( Vm =‐12±3mV; n=21). Hypotonic challenge caused a significant Vm hyperpolarisation of 11±1mV (n=9; p<0.05). We hypothesised this was due to Ca 2+ influx activating a Ca 2+ ‐activated potassium channel (K Ca ). Studies propose TRPV4 as a possible component of osmotically‐activated Ca 2+ influx so we investigated this channel. However, the TRPV4 inhibitor, RN1734, failed to prevent hypotonicity‐induced hyperpolarisation (Δ Vm =‐19±4mV, n=4; p<0.05). Application of a TRPV4 agonist, 4αPDD, caused no significant change in Vm ( n =12), whole cell current ( n =7) or cell volume ( n =8). Furthermore, application of iberiotoxin or 2‐APB completely abolished the hypotonicity‐induced hyperpolarisation. This leads us to conclude that Ca 2+ increase in response to hypotonicity is likely to result from an, as yet, unidentified range of ion channels and/or Ca 2+ stores and the K Ca channel responsible for the hyperpolarisation is a large‐K Ca channel. Grant Funding Source : Supported by European Union Seventh Framework Programme(FP7/2007‐2013) under grant agreement 305815